| Autor: |
Da Silva Filho, João, Herder, Vanessa, Gibbins, Matthew P., dos Reis, Monique Freire, Melo, Gisely Cardoso, Haley, Michael J., Judice, Carla Cristina, Val, Fernando Fonseca Almeida, Borba, Mayla, Tavella, Tatyana Almeida, de Sousa Sampaio, Vanderson, Attipa, Charalampos, McMonagle, Fiona, Wright, Derek, de Lacerda, Marcus Vinicius Guimaraes, Costa, Fabio Trindade Maranhão, Couper, Kevin N., Marcelo Monteiro, Wuelton, de Lima Ferreira, Luiz Carlos, Moxon, Christopher Alan |
| Předmět: |
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| Zdroj: |
Science Translational Medicine; 9/11/2024, Vol. 16 Issue 764, p1-18, 18p |
| Abstrakt: |
COVID-19 is characterized by a broad range of symptoms and disease trajectories. Understanding the correlation between clinical biomarkers and lung pathology during acute COVID-19 is necessary to understand its diverse pathogenesis and inform more effective treatments. Here, we present an integrated analysis of longitudinal clinical parameters, peripheral blood markers, and lung pathology in 142 Brazilian patients hospitalized with COVID-19. We identified core clinical and peripheral blood signatures differentiating disease progression between patients who recovered from severe disease compared with those who succumbed to the disease. Signatures were heterogeneous among fatal cases yet clustered into two patient groups: "early death" (<15 days until death) and "late death" (>15 days). Progression to early death was characterized systemically and in lung histopathological samples by rapid endothelial and myeloid activation and the presence of thrombi associated with SARS-CoV-2+ macrophages. In contrast, progression to late death was associated with fibrosis, apoptosis, and SARS-CoV-2+ epithelial cells in postmortem lung tissue. In late death cases, cytotoxicity, interferon, and T helper 17 (TH17) signatures were only detectable in the peripheral blood after 2 weeks of hospitalization. Progression to recovery was associated with higher lymphocyte counts, TH2 responses, and anti-inflammatory–mediated responses. By integrating antemortem longitudinal blood signatures and spatial single-cell lung signatures from postmortem lung samples, we defined clinical parameters that could be used to help predict COVID-19 outcomes. Editor's summary: A major challenge early during the COVID-19 pandemic was the inability to determine when a patient was going to recover or succumb to disease. Although vaccines, antivirals, and other therapeutics have limited the fatalities caused by COVID-19, the ability to predict disease progression remains important because it could help determine the best therapeutic approach for each patient. Here, Da Silva Filho et al. integrated antemortem peripheral blood analysis and clinical data with postmortem analysis of lung tissues to define signatures of recovery, early death, and late death from COVID-19. They then used these integrated signatures to identify peripheral blood and clinical parameters that could predict a patient's trajectory. These data could be useful for anticipating a patient's clinical course and for identifying personalized therapeutic approaches. —Courtney Malo [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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